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Positive Phase 2 Study Results of Trofinetide in Pediatric Rett Syndrome Published in Neurology, the Medical Journal of the American Academy of Neurology

March 27, 2019 Off By BusinessWire

— Statistically Significant Improvement Indicates Trofinetide’s
Potential for Treating Rett Syndrome

— Trofinetide
for Rett Syndrome has Fast Track Status and Orphan Drug Designation in
the U.S. and Orphan Drug Designation in Europe

SAN DIEGO & CINCINNATI & MELBOURNE, Australia–(BUSINESS WIRE)–ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD), Neuren Pharmaceuticals
Limited (ASX: NEU), and Rettsyndrome.org (RSO) announced today that the
positive results from a Phase 2 study conducted by Neuren, which
evaluated the safety and efficacy of trofinetide in females with Rett
syndrome (RTT), have been published in Neurology^®,
the medical journal of the American Academy of Neurology.

The study, “Double-Blind,
Randomized, Placebo-Controlled Study of Trofinetide in Pediatric Rett
Syndrome” has been published online and will appear in the April 16,
2019 issue of Neurology. The study evaluated 82 females with Rett
syndrome aged 5 to 15 years and found at the highest dose (200 mg/kg
twice daily or BID) trofinetide achieved statistically significant
improvement compared with placebo on three of five syndrome-specific
efficacy measures: the Rett Syndrome Behaviour Questionnaire (RSBQ), a
caregiver assessment (p=0.042), the Clinical Global Impression
Scale-Improvement (CGI-I), a clinician assessment of the improvement of
Rett syndrome (p=0.029), and the RTT-Clinician Domain Specific
Concerns-Visual Analog Scale (RTT-DSC), a clinician assessment
(p=0.025). Results of the study also showed trofinetide was
well-tolerated at all dose levels (50 mg/kg BID, 100 mg/kg BID, and 200
mg/kg BID).

“Disease burden is severe for Rett patients and their families, and the
impact of the disorder is life-long,” said Daniel Glaze, M.D., study
author, Baylor College of Medicine, Department of Pediatrics and
Neurology and Director at the Blue Bird Circle Rett Center, Texas
Children’s Hospital. “The data reported in this study show that females
treated with trofinetide experienced lessened neurobehavioral
impairments including social communication deficits, anxiety-like
behavior, and mood dysregulation. These are very promising data for the
Rett community that is currently without any U.S. FDA-approved treatment
option.”

In 2018, ACADIA entered into an exclusive North American license
agreement with Neuren for the development and commercialization of
trofinetide for Rett syndrome and other indications.

“Rett syndrome is a condition that leads to severe neurological
impairments and is not only debilitating for the person with the
disease, but also very hard on the families and caregivers of the
children, mostly females, who are often unable to speak, walk, eat, and
even breathe normally,” said Steve Kaminsky, Ph.D., Chief Science
Officer of RSO. “These results are very encouraging because they provide
strong evidence that trofinetide may be a potential treatment for Rett
syndrome.”

ACADIA plans to initiate a 12-week Phase 3 double-blind, randomized,
placebo-controlled study evaluating trofinetide in the second half of
2019 following completion of additional manufacturing scale-up
activities. This study will evaluate efficacy and safety of trofinetide
and placebo in approximately 180 females ages 5 to 20 years with Rett
syndrome. Half of the study participants will receive trofinetide and
half will receive placebo. The study will use the RSBQ and the CGI-I
syndrome specific efficacy measures as co-primary efficacy endpoints.
The Phase 3 study will be followed by a nine month open label extension
study in which all participants, including those on placebo in the Phase
3 study, will be eligible to receive trofinetide. In the open label
extension study, all participants will be followed to evaluate long term
tolerability and safety of trofinetide.

“Neuren has successfully led the clinical development of trofinetide to
date, which allows us to further evaluate trofinetide as a potentially
important treatment option for Rett syndrome,” said Serge Stankovic,
M.D., M.S.P.H., ACADIA’s President. “In addition to achieving successful
outcomes from early-stage clinical research with trofinetide for Rett
syndrome, Neuren has fostered strong and enduring relationships with the
Rett community. We will build on these efforts as we continue to study
trofinetide for this unmet medical need.”

Phase 2 Study Design

In the Phase 2 study, 82 females were enrolled and randomized to receive
liquid trofinetide or placebo orally or via gastrostomy tube for six
weeks: 24 subjects to placebo BID, 15 subjects to 50 mg/kg of
trofinetide BID, 16 subjects to 100 mg/kg of trofinetide BID, and 27
subjects to 200 mg/kg of trofinetide BID. Safety and tolerability
assessments included adverse events (AEs), clinical laboratory tests,
physical examinations, and concomitant medications.

The five core efficacy endpoints included three clinician-completed
measures and two caregiver-completed measures.

The RSBQ, a rating scale in which the subject’s caregiver rates the
frequency of symptoms.
The CGI-I, in which the clinician rates how much the subject’s overall
illness has improved or worsened, relative to baseline.
The RTT-DSC, in which the clinician assesses – on a visual analog
scale – the severity of concerns identified for each subject on an
individual basis.
The Motor Behavioral Assessment, a rating scale in which the clinician
rates the subject’s current level of function.
The Caregiver Top 3 Concerns, in which the subject’s caregiver
assesses – on a visual analog scale – the severity of concerns
identified for each subject on an individual basis.

About Trofinetide

Trofinetide is a novel synthetic analog of the amino‐terminal tripeptide
of IGF-1 designed to treat the core symptoms of Rett syndrome by
reducing neuroinflammation and supporting synaptic function. In the
central nervous system, IGF-1 is produced by both of the major types of
brain cells – neurons and glia. IGF-1 in the brain is critical for both
normal development and for response to injury and disease. Trofinetide
has been granted Fast Track Status and Orphan Drug Designation in the
U.S. and Orphan Drug Designation in Europe for both Rett syndrome and
Fragile X syndrome.

About Rett Syndrome

Rett syndrome is a debilitating neurological disorder that occurs
primarily in females following apparently normal development for the
first six months of life. Rett syndrome has been most often misdiagnosed
as autism, cerebral palsy, or non-specific developmental delay. Rett
syndrome is caused by mutations on the X chromosome on a gene called
MeCP2. There are more than 200 different mutations found on the MeCP2
gene that interfere with its ability to generate a normal gene product.
Rett syndrome occurs worldwide in approximately one of every 10,000 to
15,000 female births causing problems in brain function that are
responsible for cognitive, sensory, emotional, motor and autonomic
function. Typically, between six to 18 months of age, patients
experience a period of rapid decline with loss of purposeful hand use
and spoken communication and inability to independently conduct
activities of daily living. Symptoms also include seizures, disorganized
breathing patterns, an abnormal side-to-side curvature of the spine
(scoliosis), and sleep disturbances. Currently, there are no approved
medicines for the treatment of Rett syndrome.

About ACADIA Pharmaceuticals

ACADIA is a biopharmaceutical company focused on the development and
commercialization of innovative medicines to address unmet medical needs
in central nervous system disorders. ACADIA has developed and is
commercializing the first and only medicine approved for the treatment
of hallucinations and delusions associated with Parkinson’s disease
psychosis. In addition, ACADIA has ongoing clinical development efforts
in additional areas with significant unmet need, including
dementia-related psychosis, schizophrenia inadequate response,
schizophrenia-negative symptoms, major depressive disorder, and Rett
syndrome. This press release and further information about ACADIA can be
found at: www.acadia-pharm.com.

About Neuren Pharmaceuticals

Neuren Pharmaceuticals Limited (Neuren) is a biopharmaceutical company
developing new therapies for brain injury, neurodevelopmental and
neurodegenerative disorders. Neuren has completed Phase 2 development of
trofinetide for Rett syndrome and has completed a Phase 2 clinical trial
of trofinetide in Fragile X syndrome. In addition, Neuren is advancing
the pre-clinical development of its second drug candidate NNZ-2591.
Further information about Neuren can be found at: www.neurenpharma.com.

About Rettsyndrome.org

Rettsyndrome.org (RSO) is one of the leading private funders of Rett
syndrome research, investing over $46 million to date. The mission of
the organization is to accelerate full spectrum research to cure Rett
syndrome and empower families with information, knowledge and
connectivity. Rettsyndrome.org recently earned Charity Navigator’s
prestigious 4-star rating for its strong financial health and commitment
to accountability and transparency. Further information about
Rettsyndrome.org can be found at: www.rettsyndrome.org.

Forward-Looking Statements

Statements in this press release that are not strictly historical in
nature are forward-looking statements. These statements include but are
not limited to statements regarding the timing of the commencement of
the Phase 3 clinical trial evaluating trofinetide; the likelihood of
success of such clinical trial; the prospects for FDA approval of
trofinetide for Rett syndrome and other indications; and the success of
any efforts to commercialize trofinetide in North America. These
statements are only predictions based on current information and
expectations and involve a number of risks and uncertainties. Actual
events or results may differ materially from those projected in any of
such statements due to various factors, including the risks and
uncertainties inherent in drug discovery, development, approval and
commercialization. For a discussion of these and other factors, please
refer to ACADIA’s annual report on Form 10-K for the year ended December
31, 2018 as well as ACADIA’s subsequent filings with the Securities and
Exchange Commission. You are cautioned not to place undue reliance on
these forward-looking statements, which speak only as of the date
hereof. This caution is made under the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. All forward-looking
statements are qualified in their entirety by this cautionary statement
and ACADIA undertakes no obligation to revise or update this press
release to reflect events or circumstances after the date hereof, except
as required by law.